Testosterone Replacement in Men With Diabetes and Obesity

October 31, 2022 updated by: Paresh Dandona, University at Buffalo

Effect of Hypogonadotrophic Hypogonadism and Treatment With Testosterone on Insulin Sensitivity, Inflammation, Body Composition and Sexual Function in Obese and Type 2 Diabetic Men

The purpose of this study is to examine the effect of having testosterone deficiency in men with diabetes and with obesity. The study will also evaluate the effect of testosterone therapy. This will be done by comparing the changes in several body response indicators following treatment with testosterone in diabetic or obese-non diabetic men with low testosterone levels and comparing them to diabetic or obese-non diabetic men with low testosterone who are not treated with testosterone.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Hypogonadotropic hypogonadism (HH) occurs in approximately one-third of obese and type 2 diabetic men. Considering that there are 24 million diabetic and 100 million obese people, of which half are males, obesity and type 2 diabetes potentially constitute the major cause of hypogonadism in the population. We hypothesize that 1) HH in obese and type 2 diabetic men is associated with decreased insulin sensitivity, increased fat tissue mass, decreased lean body mass, increased inflammatory and oxidative stress, impaired sexual function and depressed mood as compared to diabetic and obese men with normal testosterone concentrations; and that 2) testosterone replacement for 24 weeks in men with HH leads to an improvement in these parameters. Our proposed study would be the first prospective, randomized trial to comprehensively evaluate the effect of HH on insulin sensitivity, body composition, inflammatory and oxidative indices in obese and type 2 diabetic subjects and the effect of six months of T replacement on these parameters. The study will have 2 arms (obese and type 2 diabetic arm) with 120 subjects in Diabetes arm and 80 subjects in obese arm. Half of men in each arm will have HH and half men will have normal testosterone concentrations(eugonadal men). Insulin sensitivity will be assessed by hyperinsulinemic-euglycemic clamps. Subcutaneous fat mass and lean body mass will be measured by DEXA and intra-abdominal (visceral) fat mass by MRI. All subjects will undergo hyperinsulinemic-euglycemic clamp, MRI, DEXA and give blood and urine samples (for measurement of inflammatory and oxidative stress) at baseline. Men with HH will then be randomized to receive testosterone or placebo gel for a total of 24 weeks. These men will undergo hyperinsulinemic-euglycemic clamps and give blood and urine samples for inflammation and oxidative stress at 4 weeks and 24 weeks. MRI and DEXA examinations will be carried out at 24 weeks again in men with HH. The primary endpoint of the study is to define a difference in whole body glucose uptake during hyperinsulinemic-euglycemic clamps between hypogonadal and eugonadal diabetes patients at baseline and an increase in glucose uptake in HH subjects after treatment with testosterone for 24 weeks. 30 subjects per group(testosterone and placebo gel each) will provide adequate power (0.8) to detect a significant difference of 10% in whole body glucose uptake. Therefore there will be 60 men with HH in each arm in diabetes group. For baseline comparisons, 60 men with normal testosterone concentrations will also be needed in each arm. We will recruit 40 obese patients in each arm. Thus there will be 120 diabetic men and 80 obese men in the study.

Study Type

Interventional

Enrollment (Actual)

137

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • Williamsville, New York, United States, 14221
        • 115 Flint Road

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

30 years to 65 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • T2D arm: Males with age 30-65 years
  • Obese non-diabetic arm: Obese non-diabetic males with age 30-65 years

Exclusion Criteria:

1)Coronary event or procedure(myocardial infarction, unstable angina, coronary artery bypass, surgery or coronary angioplasty) in the previous twelve weeks; 2) PSA > 4ng/ml; 3)Hemoglobin A1c > 8%; 4)h/o prostate carcinoma; 5)Hepatic disease (transaminase > 3 times normal) or cirrhosis; 6)Renal impairment (defined as GFR<30); 7)HIV or Hepatitis C positive status; 9)Participation in any other concurrent clinical trial; 10)Any other life-threatening, non-cardiac disease; 11)Use of over the counter health supplements which contain androgens; 12)Use of an investigational agent or therapeutic regimen within 30 days of study; 13)prostate nodule or severe enlargement on digital rectal examination; 14)Use of testosterone currently or in the past 4 months; 15)Hematocrit > 50%; 16)History of untreated severe obstructive sleep apnea(defined as apnea-hypopnea index ≥30); 17)symptoms suggestive of severe BPH; 18)Congestive heart failure, class III or IV; 20)Known to have anemia secondary to iron, B12 or folic acid deficiency; 21)bone marrow disorder such as myelodysplasia or aplastic anemia; 22) currently suffering from symptomatic depression, with or without treatment; 23) history of severe depression in the past which needed hospitalization; 24)currently suffering from foot ulcer, significant periodontal disease or any other chronic infectious condition; 25)planning to have children. 26) Subjects on testosterone or with testosterone replacement in the past 4 months will be excluded.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: diabetes with HH-active
Subjects with diabetes and hypogonadotropic hypogonadism. They will be randomized to testosterone intervention.
Drug: testosterone
intramuscular every 2 weeks
NO_INTERVENTION: diabetes with normal testosterone
Eugonadal subjects with diabetes. They will not be treated
ACTIVE_COMPARATOR: obese with HH-active
Obese non-diabetic men hypogonadotropic hypogonadism. They will be randomized to testosterone intervention.
Drug: testosterone
intramuscular every 2 weeks
NO_INTERVENTION: obese with normal testosterone
Eugonadal non-diabetic obese subjects. They will not be treated
PLACEBO_COMPARATOR: Diabetes with HH-placebo
Subjects with diabetes and hypogonadotropic hypogonadism. They will be randomized to placebo.
Drug: placebo
saline intramuscular every 2 weeks
PLACEBO_COMPARATOR: Obese with HH-placebo
Obese non-diabetic men hypogonadotropic hypogonadism. They will be randomized to placebo.
Drug: placebo
saline intramuscular every 2 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Insulin Sensitivity
Time Frame: baseline to 6 months
measured by HE clamps (baseline and 6 mths)
baseline to 6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Body Composition
Time Frame: baseline to 6 months
Body composition using Total body fat mass (kg)
baseline to 6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University at Buffalo

Collaborators

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2010

Primary Completion (ACTUAL)

March 1, 2015

Study Completion (ACTUAL)

November 1, 2015

Study Registration Dates

First Submitted

May 20, 2010

First Submitted That Met QC Criteria

May 20, 2010

First Posted (ESTIMATE)

May 21, 2010

Study Record Updates

Last Update Posted (ACTUAL)

November 29, 2022

Last Update Submitted That Met QC Criteria

October 31, 2022

Last Verified

October 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NIH testosterone grant
  • R01DK075877 (NIH)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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